Back to Search
Start Over
Modulation of gene expression via disruption of NF-kappaB signaling by a bacterial small molecule.
- Source :
-
Science (New York, N.Y.) [Science] 2008 Jul 11; Vol. 321 (5886), pp. 259-63. Date of Electronic Publication: 2008 Jun 19. - Publication Year :
- 2008
-
Abstract
- The control of innate immune responses through activation of the nuclear transcription factor NF-kappaB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-kappaB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-kappaB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.
- Subjects :
- 4-Butyrolactone physiology
Adult
Animals
Cyclic AMP Response Element-Binding Protein metabolism
Cystic Fibrosis microbiology
Female
Homoserine physiology
Humans
I-kappa B Kinase metabolism
I-kappa B Proteins metabolism
Immunity, Innate
Interferon-gamma immunology
Lipopolysaccharides immunology
Macrophage Activation
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
NF-KappaB Inhibitor alpha
Phosphorylation
Pseudomonas Infections immunology
Pseudomonas Infections microbiology
Pseudomonas aeruginosa immunology
Pseudomonas aeruginosa physiology
Toll-Like Receptors metabolism
Transcription Factor RelA metabolism
4-Butyrolactone analogs & derivatives
Gene Expression Regulation
Homoserine analogs & derivatives
Macrophages immunology
Macrophages metabolism
NF-kappa B metabolism
Pseudomonas aeruginosa pathogenicity
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 321
- Issue :
- 5886
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 18566250
- Full Text :
- https://doi.org/10.1126/science.1156499